Clinical Disparities in COVID-19 Presentation, and Outcomes: A Comparative Study of Pediatric Immunocompetent and Cancer Patients, A Single Center Experience

doi:10.21203/rs.3.rs-4335301/v1

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Research Article

Clinical Disparities in COVID-19 Presentation, and Outcomes: A Comparative Study of Pediatric Immunocompetent and Cancer Patients, A Single Center Experience

https://doi.org/10.21203/rs.3.rs-4335301/v1

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Introduction:

This research study focused upon COVID-19 impact on pediatric patients, particularly those with a history of cancer. The study examined the prevalence of COVID-19 among children, the severity of the disease, and its complications. This study aimed to determine whether pediatric patients with a history of cancer are at a greater risk for severe COVID-19. This study also addressed the scarcity of data on this topic and intended to provide valuable insights into infection outcomes among children with COVID-19 and cancer history.

Methods

The study was conducted on COVID-19 pediatric patients at the Princess Noorah Oncology Center at King Abdulaziz Medical City (KAMC), Jeddah, Saudi Arabia. The data were collected as a part of a retrospective study design on a cohort of COVID-19-positive patients, using the “Best Care system” electronic medical records files, from January 2020 to December 2022. A total of 210 patients were included in this study. Descriptive, comparative, and regression analyses were applied to examine differences in demographic / clinical characteristics and COVID-19 morbidity / mortality between patients with / without cancer.

Results

In terms of COVID-19 symptoms, a significant difference was observed in the presence of fever, with 52.7% of immunocompetent individuals, and 82.1% of cancer patients experiencing fever. There was also a significant difference in diarrhea symptoms; 14.8% of the patients were immunocompetent, and none of the patients with cancer had diarrhea. Hemoglobin levels and neutrophil counts were lower in the cancer group than in the immunocompetent group. Additionally, the lymphocyte counts were lower in the cancer group. Findings from radiological studies indicated that differences in peribronchiolar thickening were greater in the immunocompetent group. The results showed that 10.7% of COVID-19-positive cancer patients died, while none of the immunocompetent patients with COVID-19 died.

Conclusions

This study provides valuable insights into the disparities in COVID-19 characteristics, symptoms, treatments, and outcomes between immunocompetent individuals and cancer patients. These findings could contribute to a better understanding of how COVID-19 affects different patient populations, and inform clinical decision-making. It is important to consider these results in the context of limitations and implications for future research and medical practices.

COVID-19 clinical outcomes

COVID-19 presentation

clinical disparities

comparison study

immunocompetent patients

pediatric cancer patients

Saudi Arabia

The emergence of coronavirus (COVID-19) infection, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), had profound implications for global healthcare systems since its outbreak in December 2019 (1, 2). Notably, pediatric cases of COVID-19 tend to exhibit milder symptoms when compared to adults, possibly due to differences in inflammatory responses between adult and pediatric immune systems. A critical determinant of COVID-19 severity is the presence of Angiotensin Converting Enzyme-2 (ACE2) cell receptors, which the SARS-CoV-2 virus utilizes for cellular entry (3). Importantly, children typically express fewer ACE2 receptors, potentially contributing to their reduced susceptibility to severe COVID-19 outcomes (4). During the early stages of the pandemic, data regarding pediatric COVID-19 cases were limited, partly due to overlap with upper respiratory tract infections, and the ongoing development of pediatric immune systems (5). Despite representing a relatively small proportion of COVID-19 cases (1.7%), over 90% of children under 18-years displayed asymptomatic, mild, or moderate disease, with a minority (5.2%) experiencing severe symptoms, and an even smaller fraction (0.6%) developing critical illness (6–8). Notably, children aged 9 years and younger exhibited no fatalities in a study conducted in China (7–9).

However, pediatric oncology patients, due to their immunocompromised state, are at risk of COVID-19 complications. While milder cases dominated pediatric COVID-19 data, severe outcomes were documented in pediatric oncology patients, emphasizing the need for further investigation (10). Reports indicated that SARS-CoV-2 infection in children and young individuals seldom led to severe outcomes or death (11). Nevertheless, those who experienced severe illness often encountered multi-organ and autoimmune complications persisting for weeks or months post-COVID-19 (4). This condition is presently defined as a complication of COVID-19 infection and is termed as multisystem inflammatory syndrome in children (MIS-C) (12–14). Early evidence from Chinese pediatric patients pointed that cancer and chemotherapy were potential risk factors for severe illness (15). Furthermore, research by the French Society of Pediatric Oncology (SIOP) identified serious complications in five out of 33 pediatric oncology patients with COVID-19 (16). Increased mortality and hospitalization rates were also noted in the Pediatric Oncology COVID Case Report (POCC Report) and the St. Jude Children's Research Hospital global registry (17). These findings underscored the elevated risk faced by pediatric oncology patients with COVID-19, when compared to their immunocompetent counterparts.

Notably, no previous local studies have compared COVID-19 outcomes between pediatric cancer patients and immunocompetent pediatric patients in this region.

This study aims to bridge this gap by analyzing data from pediatric COVID-19 patients, differentiating between those with a history of cancer and those without. By recognizing disparities in symptom severity, infection outcomes, and duration between these two cohorts, this study seeks to enhance current knowledge of how COVID-19 impacts pediatric oncology patients. This knowledge is pivotal for informing future research initiatives, both at the national and global levels, and for developing effective treatment strategies for this vulnerable population.

Study Design and Patient Data

A retrospective study was designed to analyze a patient cohort screened for COVID-19 at King Abdulaziz Medical City (KAMC-J) in Jeddah, Saudi Arabia. Patient data were obtained from the “Best Care” System and medical records covering the period from 2020 to 2022. A total of 210 patients were included in this investigation. COVID-19 testing was exclusively conducted on pediatric patients who presented with fever, or symptoms indicative of respiratory illness. Patients met specific criteria, including recent travel to pandemic-affected regions (such as Iran, China, Japan, Italy, and South Korea), or direct contact with a confirmed COVID-19 patient within the previous two weeks. The analysis included all patients who tested positive for COVID-19 between January 2020 and December 2022. Within KAMC-J, respiratory specimens from COVID-19 patients were evaluated using real-time reverse transcription-polymerase chain reaction (RT–PCR) methods, according to the World Health Organization (WHO) protocol. In addition, immunocompetent pediatric patients were identified and segregated into the immunocompetent cohort through a series of diagnostic evaluations, which included criteria such as the absence of cancer or other autoimmune diseases, as well as not being on active immunosuppressive agents.

Statistical analysis

The statistical analysis aimed to compare the vital signs, symptoms, laboratory findings, radiological findings, treatments received, and complications of pediatric cancer patients with COVID-19 against those of immunocompetent COVID-19-positive patients without a history of autoimmune diseases or cancer.

Descriptive Statistics

Descriptive statistics were used to summarize study characteristics. Frequencies and percentages were calculated for categorical variables, such as symptoms, radiological findings, treatments received, and complications of COVID-19. Continuous variables, such as vital signs and laboratory findings, were assessed for normality using mean and standard deviation calculations. To evaluate the non-normality of the data, the median and interquartile range (IQR) were calculated.

Inferential Statistics

To compare certain categorical variables between the two groups (cancer and immunocompetent COVID-19 pediatric patients), Fisher’s exact test was used. Differences between the two groups for continuous variables were analyzed using the independent sample t test, and the Mann‒Whitney U test. The Mann‒Whitney U test was chosen for variables with non-normal distributions, as determined by the Shapiro‒Wilk test (p < 0.05). The statistical tests aimed to identify statistically significant differences in vital signs, symptoms, laboratory findings, radiological findings, treatments received, and complications of COVID-19 between the two groups.

Significance Testing

Significance was tested at a p-value of 5% (or less) and a 95% confidence interval. All statistical calculations where performed using IBM™ SPSS Statistics®.

There were 210 individuals in all, 28 of whom had cancer, and 182 of whom were immunocompetent. Table 1 displays the sociodemographic details and health-related variables of participants across two different categories: cancer patients and immunocompetent patients. Regarding age distribution, most participants in the immunocompetent group (49.5%) were under 5 years old, whereas the majority in the cancer group (53.6%) were between 5 and 10 years old. The gender distribution was fairly balanced, with slightly more males (53.3%) and slightly more females (53.6%) in the immunocompetent group and cancer group, respectively. According to statistical evaluations, 5 of the 182 immunocompetent patients had diabetes, whereas no cancer patients had this disease. Additionally, hypertension was observed in one of the 182 immunocompetent patients, and three out of the 28 cancer patients were receiving corticosteroids and chemotherapy. Furthermore, nine patients in the immunocompetent group developed obesity, while just three had cancer, and 16.5% of the patients in the immunocompetent group developed asthma.

Table 1

Sociodemographic Characteristics and Health Related Factors of Participants in The Study.
		Immunocompetent Group		Cancer Group		Total
		N = 182	N %	N = 28	N %	N = 210
Age	< 5 years	90	49.5%	5	17.9%	95
	5–10 years	63	34.6%	15	53.6%	78
	> 10 years	29	15.9%	8	28.6%	37
Gender	Male	97	53.3%	13	46.4%	110
Gender	Female	85	46.7%	15	53.6%	100
Nationality	Saudi	178	97.8%	28	100.0%	206
Nationality	non-Saudi	4	2.2%	0	0.0%	4
Diabetes	No	176	97.2%	28	100.0%	204
Diabetes	Yes	5	2.8%	0	0.0%	5
Hypertension	No	181	99.5%	25	89.3%	206
Hypertension	Yes	1	0.5%	3	10.7%	4
Asthma	No	152	83.5%	28	100.0%	180
Asthma	Yes	30	16.5%	0	0.0%	30
Obesity	No	171	95.0%	25	89.3%	196
Obesity	Yes	9	5.0%	3	10.7%	12

Table 2 provides descriptive statistics for cancer patients, in terms of their presentation status, type and stage of cancer and treatment modalities received. Among the cancer patients, 32.1% were newly diagnosed, 46.4% were in remission, 14.3% had relapsed, and 7.1% were in the maintenance phase of chemotherapy. The most prevalent type of cancer was acute lymphocytic leukemia (ALL) (69.2%), followed by acute myeloid leukemia (AML) (7.7%), central nervous system (CNS) tumors (7.7%), and sarcoma tumors (7.7%). Lymphoma and neuroblastoma constituted 3.8%. Concerning solid tumor staging, one patient (33.3%) was in stage 3, and two patients (66.7%) were in stage 4. Regarding treatment modality, 3 out of 28 (10.7%) patients underwent surgery. Only 2 out of 27 patients (7.4%) received radiation treatment. All patients (100.0%) received chemotherapy, and 5/23 (17.9%) underwent stem cell transplantation. Only 3 out of 27 patients (11.1%) received biologic therapy.

Table 2

Descriptive Statistics of Cancer Patients.
		n	N %
Status of presentation	newly diagnosed	9	32.1%
	remission	13	46.4%
	relapsed	4	14.3%
	maintenance	2	7.1%
Type of cancer	ALL	18	69.2%
	AML	2	7.7%
	Lymphoma	1	3.8%
	CNS tumor	2	7.7%
	Neuroblastoma	1	3.8%
	Sarcoma	2	7.7%
Stage of cancer	stage I	0	0.0%
	stage II	0	0.0%
	stage III	1	33.3%
	stage IV	2	66.7%
Treatment modality
Surgery	no	25	89.3%
Surgery	yes	3	10.7%
Radiation	no	25	92.6%
Radiation	yes	2	7.4%
Chemotherapy	no	0	0.0%
Chemotherapy	yes	28	100.0%
Stem cell transplant	no	23	82.1%
Stem cell transplant	yes	5	17.9%
Biological	no	24	88.9%
Biological	yes	3	11.1%

Table 3 presents a comparison of vital signs between the immunocompetent and cancer groups, indicating medians and interquartile ranges (IQRs), along with the associated p-values for each parameter. The median temperature for the immunocompetent group was 36.90°C, with an IQR of 36.70°C to 37.40°C, while the median temperature was 37.20°C and an IQR of 36.90°C to 38.10°C for the cancer group. The p-value of 0.014 suggested a statistically significant difference in temperature between the two groups. Concerning heart rate, both groups displayed a median of 120 beats per minute, and there was no significant difference between them. The median systolic blood pressure (SBP) was 102 mmHg for the immunocompetent group and 101 mmHg for the cancer group, and the difference was not statistically significant. Similarly, diastolic blood pressure (DBP) was not significantly different between both groups. The respiratory rate was a median of 27 breaths per minute in the immunocompetent group (IQR: 22 to 40 breaths per minute), and a median of 24 breaths per minute in the cancer group (IQR: 22 to 28 breaths per minute). A p-value of 0.030 indicated a statistically significant difference in respiratory rate between the two groups. Oxygen saturation (oxygen) did not significantly differ between the two groups.

Table 3

Comparison of Vitals Between Immunocompetent and Cancer Groups.
	Immunocompetent Group		Cancer Group
	Median	IQR	Median	IQR	P value
Temperature	36.90	36.70– 37.40	37.20	36.90–38.10	0.014*
Heart rate	120	104–147	120	102–137	0.626
SBP	102	92–112	101	95–109	0.709
DBP	58	51–65	61	52–69	0.470
Respiratory rate	27	22–40	24	22–28	0.030*
oxygen	99	98–100	99	99–100	0.126
*p < 0.05, significant

Table 4 presents a comparison of COVID-19 symptoms between the immunocompetent and cancer groups. The presence of fever was significantly different between the two groups, with 52.7% of immunocompetent individuals and 82.1% of cancer patients experiencing fever (p value = 0.004*). There was no significant difference in the incidence of rhinorrhea, with 26.9% of immunocompetent patients and 17.9% of cancer patients reported this. Similarly, no significant differences were detected for sore throat, cough, respiratory distress, vomiting, shortness of breath, hypoxia, anosmia, ageusia, myalgia, fatigue, seizure, skin manifestations, shock, or decreased oral intake. However, diarrhea symptoms were significantly different between the two groups. Among the immunocompetent individuals, 14.8% had diarrhea, though none of the cancer patients had diarrhea (p value = 0.030*).

Table 4

Comparison of Symptoms COVID 19 Between Immunocompetent and Cancer Groups.
		Immunocompetent Group		Cancer Group
		n	%	n	%	P value
Fever	No	86	(47.3)	5	(17.9)	0.004*
Fever	Yes	96	(52.7)	23	(82.1)	0.004*
Runny nose	No	133	(73.1)	23	(82.1)	0.362
Runny nose	Yes	49	(26.9)	5	(17.9)	0.362
Sore throat	No	161	(88.5)	25	(89.3)	> 0.99
Sore throat	Yes	21	(11.5)	3	(10.7)	> 0.99
Cough	No	115	(63.2)	16	(57.1)	0.537
Cough	Yes	67	(36.8)	12	(42.9)	0.537
Respiratory distress	No	165	(90.7)	28	(100.0)	0.136
Respiratory distress	Yes	17	(9.3)	0	(0.0)	0.136
Vomiting	No	141	(77.5)	26	(92.9)	0.077
Vomiting	Yes	41	(22.5)	2	(7.1)	0.077
Diarrhea	No	155	(85.2)	28	(100.0)	0.030*
Diarrhea	Yes	27	(14.8)	0	(0.0)	0.030*
SOB	No	156	(85.7)	27	(96.4)	0.139
SOB	Yes	26	(14.3)	1	(3.6)	0.139
Hypoxia	No	175	(96.7)	27	(96.4)	> 0.99
Hypoxia	Yes	6	(3.3)	1	(3.6)	> 0.99
Anosmia	No	182	(100.0)	27	(96.4)	0.133
Anosmia	Yes	0	(0.0)	1	(3.6)	0.133
Ageusia	No	182	(100.0)	28	(100.0)
Myalgia	No	173	(95.1)	26	(92.9)	0.644
Myalgia	Yes	9	(4.9)	2	(7.1)	0.644
Fatigue	No	163	(89.6)	26	(92.9)	0.747
Fatigue	Yes	19	(10.4)	2	(7.1)	0.747
Seizure	No	169	(92.9)	27	(96.4)	0.699
Seizure	Yes	13	(7.1)	1	(3.6)	0.699
Skin manifestations	No	174	(95.6)	27	(96.4)	> 0.99
Skin manifestations	Yes	8	(4.4)	1	(3.6)	> 0.99
Shock	No	182	(100.0)	27	(96.4)	0.133
Shock	Yes	0	(0.0)	1	(3.6)	0.133
Decreased oral intake	No	136	(74.7)	23	(82.1)	0.483
Decreased oral intake	Yes	46	(25.3)	5	(17.9)	0.483
*p < 0.05, significant

Table 5 presents a comparison of laboratory findings between the immunocompetent and cancer groups. Specifically, hemoglobin levels were significantly different across groups, with means of 12.3 and 10.2 for the immunocompetent and cancer groups, respectively (p-value < 0.001*). Neutrophil counts also exhibited a significant difference, with a mean of 4.18 for the immunocompetent group, and 2.05 for the cancer group (p value = 0.013*). Other laboratory findings, such as glucose, fibrin, partial thromboplastin time (PTT), platelet count (PLT), alanine transaminase (ALT), lactic acid, prothrombin time (PT), D-dimer, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, aspartate transaminase (AST), creatinine (CRET), and bilirubin, showed no significant variations across both groups. Lymphocyte counts, however, exhibited a significant difference, with a median of 3.21, an IQR of 2.07–5.85 for the immunocompetent group, against a median of 1.23 and an IQR of 1.23 to 1.73 for the pediatric cancer group (p-value < 0.001*).

Table 5

Comparison of Lab Findings Between Immunocompetent and Cancer Groups.
	Immunocompetent Group				Cancer Group
	Mean	SD	Median	IQR	Mean	SD	Median	IQR	P value
Hemoglobin	12.3	2.1			10.2	2.4			< 0.001*
Neutrophils	4.18	3.93			2.05	3.78			0.013*
Glucose	5.66	2.27			5.82	1.35			0.732
Fibrin	3.33	1.24			2.77	.47			0.456
PTT	35.48	8.55			33.20	1.48			0.557
Platelet	368.63	163.24			160.29	92.36			0.963
ALT	30.22	91.04			35.83	40.24			0.799
Lymphocytes			3.21	2.07–5.85			1.23	0.65–1.73	< 0.001*
Lactic acid			1.96	1.00–3.20			2.20	1.00–3.39	1.000
Pt			12	11–13			12.00	12.00–12.00	0.894
D dimer			0.90	0.30–2.10			0.37	0.32–1.04	0.464
CRP			4.35	1.10–17.75			5.10	3.80–17.70	0.193
ESR			16.5	6.0–34.0			29.00	29.00–29.00	0.405
Pro calcitonin			0.08	0.04 -0 .12			0.21	0.10–0.65	0.153
AST			34.00	26.50–45.00			31.00	21.00–40.00	0.186
CRET			41	37–51			43.00	39.00–46.00	0.939
Bilirubin			5.70	3.90–8.80			7.50	5.50–9.70	0.127
*p < 0.05, significant

Table 6 compared the radiological findings between immunocompetent patients and cancer patients. Ground-glass opacity was observed in 4.3% of the immunocompetent patients, though not in any of the cancer patients. Similarly, patchy consolidations were found in 3.1% of immunocompetent individuals, though not in any of the cancer patients. Air bronchograms were present in 0.6% of immunocompetent individuals, though were absent in cancer patients. Peribronchiolar thickening was observed in 23.5% of immunocompetent individuals and 3.8% of cancer patients (p = 0.019). Adjacent pleura thickening was identified in 1.8% of immunocompetent individuals, though was not observed in cancer patients. Bilateral lung involvement was present in 6.1% of immunocompetent patients, though was absent in cancer patients. Reticular appearances and fibrosis were rare in both groups (percentages at < 2%). Interlobular septal thickening was identified in 1.3% of immunocompetent patients, though was not found in cancer patients.

Table 6

Comparison of Radiological Findings Between Immunocompetent and Cancer Groups
		Immunocompetent Group		Cancer Group
		n	N %	n	N %	P value
Ground-glass opacity	No	156	95.7%	25	100.0%	0.597
Ground-glass opacity	Yes	7	4.3%	0	0.0%
Patchy consolidations	No	158	96.9%	25	100.0%	> 0.99
Patchy consolidations	Yes	5	3.1%	0	0.0%
Air bronchogram	No	162	99.4%	25	100.0%	> 0.99
Air bronchogram	Yes	1	0.6%	0	0.0%
Peri bronchiolar thickening	No	127	76.5%	25	96.2%	0.019*
Peri bronchiolar thickening	Yes	39	23.5%	1	3.8%
Adjacent pleura thickening	No	160	98.2%	25	100.0%	> 0.99
Adjacent pleura thickening	Yes	3	1.8%	0	0.0%
Bilateral lung involvement	No	154	93.9%	25	100.0%	0.364
Bilateral lung involvement	Yes	10	6.1%	0	0.0%
reticular appearance	No	161	98.8%	25	100.0%	> 0.99
reticular appearance	Yes	2	1.2%	0	0.0%
Fibrosis	No	161	98.8%	25	100.0%	> 0.99
Fibrosis	Yes	2	1.2%	0	0.0%
interlobular septal thickening	No	152	98.7%	25	100.0%	> 0.99
interlobular septal thickening	Yes	2	1.3%	0	0.0%
*p < 0.05, significant

Figure 1 presents a descriptive comparison of COVID-19 treatment regimens between immunocompetent individuals and cancer patients. These findings indicated notable differences in treatment approaches. None of the cancer patients required supplemental oxygen, while 7.6% of immunocompetent patients received supplemental oxygen. Mechanical ventilation was used in 0.6% of immunocompetent patients, though not in cancer patients. Nebulizer treatment was administered to 14.9% of immunocompetent patients, though not to any of the cancer patients. Antibiotic usage differed, with co-amoxiclav (Augmentin®) not used in cancer patients, though administered to 6.4% of immunocompetent patients, while ceftriaxone was employed more frequently in cancer patients (38.5%) than in immunocompetent patients (14.5%). Remdesivir, analgesics, and dexamethasone were not used in cancer patients, though a minor percentage of immunocompetent patients received such treatments (1.2%, 10.4%, and 6.9%, respectively). Antipyretics were utilized by a greater percentage of cancer patients (57.1%) than immunocompetent patients (44.1%). These findings suggest variations in disease severity, respiratory support needs, and medication choices, based upon immunocompetence and the underlying cancer condition.

Table 7 compares short-term COVID-19 outcomes (PICU, morbidity, and mortality rates) between the immunocompetent and cancer groups. There was no significant difference in the rates of pediatric intensive care unit (PICU) admission (8.5% vs 7.1%, p = 1.000) or morbidity (6.6% vs 7.1%, p = 1.000) between the two groups. None of the 28 cancer patients had any signs or symptoms of pediatric multisystem inflammatory syndrome (PIMS) or post-infectious COVID-19-associated multisystem inflammatory syndrome in children (MIS-C). There were no indications of multiorgan system involvement or neurological, cardiac, or severe pulmonary issues. The gastrointestinal symptoms experienced by cancer patients were only temporary. According to Table 7, the mortality rate was significantly higher in cancer patients (10.7%) when compared to immunocompetent individuals, where no deaths were reported.. This suggests that COVID-19 had a more severe impact on cancer patients, increasing their likelihood of mortality event occurrence. The immunocompetent group’s ability to mount an immune response likely contributed to their reduced mortality rate. The absence of mortality events in the immunocompetent group can be attributed to their effective response to COVID-19 complications, which prevent fatal outcomes (18). In contrast, mortality events occurred among cancer patients, particularly those with a history of stem cell transplantation, indicating that preexisting cancer diagnoses and treatments were contributing factors to the higher mortality rate (19).

Table 7

Comparison of COVID-19 Outcomes Between Immunocompetent and Cancer groups.
		Immunocompetent Group		Cancer Group
		n	N %	n	N %	P value
PICU	No	162	91.5%	26	92.9%	> 0.99
PICU	Yes	15	8.5%	2	7.1%
Morbidity	No	170	93.4%	26	92.9%	> 0.99
Morbidity	Yes	12	6.6%	2	7.1%
Mortality	No	182	100.0%	25	89.3%	0.002*
Mortality	Yes	0	0.0%	3	10.7%
*p,0.05, significant

Further evaluations included IQR-based descriptive statistics for multiple clinical parameters monitored across all patients (Table 8), together with binary logistic regression analyses for main clinical parameters and symptoms (Table 9).

Table 8

Descriptive statistics (IQR)
	N	Mean	SD	Median	IQR		Minimum	Maximum
Age	182	70.5	46.7	60.0	34	108	8	180
Temperature	177	37.2	0.8	36.9	36.7	37.4	36.1	40.2
Heart rate	171	123.6	27.1	120.0	104	147	26	184
SBP	133	110.0	89.1	102.0	92	112	56	1116
DBP	134	58.7	11.2	58.0	51	65	36	95
Respiratory rate	173	34.0	23.6	27.0	22	40	18	288
Oxygen	174	98.3	2.4	99.0	98	100	83	100
Hg	112	12.3	2.1	12.4	11.0	13.5	7.1	18.5
Neut	111	4.2	3.9	3.0	1.6	5.2	.32	22
Lympho	112	11.3	61.6	3.2	2.1	5.9	.57	650
Lactic acid	16	22.2	80.2	2.0	1.0	3.5	.95	323
Blood glucose	112	5.7	2.3	5.4	4.5	6.3	1.7	21.2
Fibrin	19	3.3	1.2	3.1	2.8	3.5	1.2	6.9
Ptt	52	35.5	8.5	34.0	30	39	24	76
Pt	52	12.2	2.0	12.0	11	13	1	16
d dimer	38	1.6	1.8	1.0	0.3	2.2	.1	7.7
Plt	111	368.6	163.2	343.0	264	470	1	911
CRP	100	16.5	33.1	4.4	1.1	18.0	.2	218.4
ESR	24	25.8	31.4	16.5	5.5	38.0	2	120
ALT	85	30.2	91.0	19.0	12.0	23.5	8	850
procalcitonin	76	0.2	0.7	0.1	0.0	0.1	.02	4.50
AST	83	49.4	98.1	34.0	27	45	9	913
CRET	107	46.3	22.6	41.0	37	51	30	222
Bilirubin	85	17.5	36.4	5.7	3.9	9.1	1.8	198.8

Table 9

Test statistics (Binary Logistic Regression Analyses)
		B	S.E.	Wald	df	p-value	Odds Ratio		95% CI
Fever
	No	.361	1.330	.074	1	.786	1.435	.106	19.451)
	Yes	Ref
Diarrhea
	No	-22.373	9095.912	.000	1	.998	.000	.000
	Yes	Ref
Peri-bronchial thickening
	No	-21.355	8542.068	.000	1	.998	.000	.000
	Yes	Ref
Mortality
	No	21.229	3325.768	.000	1	.995	1657869022.928	.000
	Yes	Ref
Temperature		.249	.485	.263	1	.608	1.282	.496	3.316
Respiratory rate		.028	.049	.326	1	.568	1.029	.934	1.133
Hemoglobin		.809	.304	7.078	1	.008	2.245	1.237	4.073
Neutrophils		.087	.108	.652	1	.419	1.091	.883	1.349
Lymphocytes		1.939	.678	8.187	1	.004	6.952	1.842	26.239

The overall model was significant at the 1% level, as shown by the chi-square statistic. The variables included in the model explained 66.6% of the dependent variable (type of patient, whether cancer or immunocompetent). The estimated model correctly classified 93.5% of the patients in the two categories of the dependent variable. Hb levels and lymphoma status were significant predictors of the dependent variable. Patients with a hg reading were 2.245 times more likely to be immunocompetent patients. Patients with lymphoma were 6.952 times more likely to be immunocompetent.

The aim of the study was to compare COVID-19 outcomes between pediatric patients with cancer and immunocompetent patients. A total of 210 participants were included in the study. Age distribution and gender balance between groups differed. The study looked into the incidence of various health-related factors, including diabetes, hypertension and asthma. Minor disparities were noted in these factors between the two groups, with slightly higher percentages of certain health conditions observed in the cancer group. For example, the substantial disparities in the obesity findings presented in Table 1 can be attributed to two main factors, attributed to limitations of using the body mass index (BMI) and growth chart data as a reliable indicator for accurate assessment of obesity. The study's findings reveal intriguing insights into the comparison of vital signs and COVID-19 symptoms between the immunocompetent and cancer cohorts. In terms of vital signs, it was observed that the cancer group exhibited significantly higher body temperatures in comparison to the immunocompetent group. This discrepancy may suggest a plausible correlation between cancer and elevated body temperatures. Previous studies have also reported similar observations, noting elevated temperatures among cancer patients during COVID-19 infection (20, 21). Such temperature fluctuations may be attributed to the complex physiological dynamics associated with cancer, potentially influencing the body's response to infections and other stressors, thus resulting in more pronounced temperature elevations (20, 21). Nevertheless, there was no statistically significant difference between the groups in terms of heart rate and blood pressure. However, there was a statistical difference in respiratory rates that was yielded by analysis, potentially due to cancer. Also, a striking degree of difference was observed in the incidence of diarrhea; immunocompetent patients were more likely to contract such a symptom. This in turn could potentially affect the occurrence of symptoms commonly associated with COVID 19, such as diarrhea, which may be attributed to various underlying mechanisms associated with the cancer itself, including potential alterations in immune responses or physiological changes linked to the cancer or its therapeutic interventions (22). However, this study’s identified differences contrast with an investigation performed in 2010 by Stein et al., that found elevated rates of diarrhea among cancer patients (23). These differences could possibly be attributed to variations in the populations studied and underlying medical conditions in terms of contracting diarrhea symptom (23). Regarding laboratory findings, notable distinctions emerged in hemoglobin levels, neutrophil and lymphocyte counts. When comparing the two groups, the immunocompetent group exhibited elevated levels, in contrast to the cancer group. These variations may stem from the intricate interplay between cancer, COVID-19 and chemotherapy provided (24). Among the radiological findings between the two groups, several differences were noted. Ground-glass opacity, patchy consolidations and air bronchogram were more common in the immunocompetent group, while peribronchiolar thickening findings were the most significant. This may be due to lung abnormalities that are particularly pronounced and widespread among individuals without a pre-existing cancer condition during COVID-19 infection (24–26). The absence of these radiological findings in cancer patients is likely a result of their intrinsically immunodeficient state and differing disease manifestations (25, 26). Bilateral lung involvement was more common in the immunocompetent group, whereas it was absent in cancer patients. Similarly, the differences in adjacent pleura thickening and interlobular septal thickening suggest variations in the impact of COVID-19 on the respiratory system, based on the patient’s immune / cancer status (26). The comparison of COVID-19 treatments and outcomes between the immunocompetent and cancer groups in this study provides a comprehensive understanding of the impact of cancer on management and patient outcomes. In terms of treatments, differences between the groups were observed in several aspects. The absence of supplemental oxygen and mechanical ventilation in cancer patients suggests potential differences in disease severity and treatment approaches. Nebulizer treatment and antibiotic usage also exhibited distinct patterns, with lower rates in cancer patients. The usage of specific medications, such as ceftriaxone, azithromycin, and remdesivir varied between the two groups, likely reflecting tailored treatment strategies, based on the presence of cancer. The differences in dexamethasone, analgesics, and antipyretic usage highlight variations in symptom management strategies between the two groups. Notably, the absence of certain medications, such as remdesivir and dexamethasone in cancer patients, might be due to concerns about potential interactions or complications in this population (22).

In terms of clinical outcomes, admission rates to PICU and overall morbidity rates showed similar trends between the immunocompetent and cancer cohorts, suggesting that COVID-19's impact on disease severity did not significantly differ based on cancer status (22, 24). However, the most significant distinction arose in terms of mortality. Although no fatalities were reported among the immunocompetent patients, a worrisome 10.7% of cancer patients died. The high mortality of pediatric cancer patients with COVID-19 is due to a number of factors. Their weakened immune system, caused by cancer and chemotherapy, and the physiological impact of the cancer itself, can make for more dire results. Cancer and its treatments significantly suppress the immune system, making patients more susceptible to infections that would otherwise be less threatening (27).

This susceptibility often leads to serious complications. Fever and diarrhea were also more common in the cancer group, according to previous studies found in the literature, suggesting greater levels of viral replication involving multiple organs (23). Immune responses against cancer, available cancer treatment exposure or the mechanisms involved in a cancer's microenvironment may affect how the virus replicates and spreads through the body. Furthermore, when cancer advances, the body could develop resistance to treatment, and cancer spreads unbridled. Understanding these factors is important in improving outcomes for this vulnerable population. Although they had weakened immune systems due to cancer and chemotherapy, they did not show any signs of multisystem inflammatory syndrome in children (MIS-C) or post-infectious COVID-19.

Owing to pediatric cancer, according to the nature of their underlying disease and the cancer treatment-related weakened immune systems, peculiar responses result that can influence this unique population’s response to the novel coronavirus, COVID-19 (28). They might even be at increased risk of developing MIS-C. However, as pediatric cancer patients are already in the course of receiving standard medical treatment, the early warning signs of MIS-C exhibited might not be as noticed as in immunocompetent patients associated with a recurrent history of COVID-19. In these patients, early detection and medical treatment has prevented the spread of infection; mortality is thus greatly reduced. Therefore, cancer treatments should be regulators of the immune response, as they weaken the immune system. These changes induced by treatment might even influence the body's inflammatory response–prompting us to reconsider MIS-C. Furthermore, when these pediatric cancer patients with COVID-19 displayed gastrointestinal symptoms, they had no systemic transmission (to the heart) or neurovascular involvement. There was no serious damage to the lungs, either. This means that cancer patients are not more prone than others to severe cases of MIS-C or pediatric inflammatory multisystem syndrome (PIMS), caused by post-infectious COVID19.

In essence, the study showed that pediatric cancer patients differed vastly from immunocompetent people with regard to demographic factors, symptoms and signs of COVID-19 infection. Their laboratory findings often were atypical or absent entirely; radiological features typically resembled those found in the other group. Compared to immunocompetent individuals, pediatric cancer patients' development of symptoms were higher, their laboratory and radiological findings were distinctly different; mortality was increased. However, disease severity did not differ between the groups. These differences probably reflect the unique immune ecosystem of these patients, which is shaped in turn by their underlying diseases and therapies. Well-coordinated early diagnosis, time-limited intervention and continued precautions are all important for the management of COVID-19 in this vulnerable population. Still, further research with larger samples is needed to corroborate these results and better understand the effect of COVID-19. Pediatric cancer patients may be at higher risk for worse outcomes from COVID-19 infection. The public should continue taking precautionary measures to avoid contracting the virus, as well as checking with health care providers if any suspicious symptoms arise.

Nonetheless, this study has several limitations. The small number of actual cases limits the extent to which we can extrapolate our findings to a larger population. Some bias is possible due to the retrospective design and reliance on medical records. Given the study's focus on a specific region and population, its results cannot be generalized to different geographic areas or patient populations. Additionally, the study did not control for potential confounding variables and lacked long-term follow-up, which could have impacted the results. Under such limits, these findings can be replicated and expanded upon through larger research sample sizes and more diverse populations.

Advantages

The present study offers several advantages, including a comparative analysis between pediatric cancer patients and immunocompetent patients with COVID-19 infection. It also offers insights into the challenges faced by pediatric cancer patients, who are unique and different from people without a compromised immune system. This study comprehensively analyzed many factors, including demographic characteristics, symptoms and signs of illness, laboratory findings, radiological features, and treatment approaches. Moreover, the study’s clinical relevance and focus on mortality rates highlight the greater risk faced by pediatric cancer patients and provide practical implications for healthcare providers. The research also revealed different trends. For instance, the illness shows distinctive symptoms and variations in immune physiology responses, contributing to a deeper understanding of the impact of COVID-19 on pediatric cancer patients and informing targeted interventions and preventive measures.

This study provides valuable insights into the disparities in COVID-19 characteristics, symptoms, treatments, and outcomes between immunocompetent patients and pediatric cancer patients. By understanding these features, effective interventions and decisions can be made regarding medication related to cancer. This research aimed to compare the impact of COVID-19 on pediatric patients with cancer and those without immune deficiencies.

The study, involving 210 participants, compared the presentation and outcomes of COVID-19 in pediatric cancer patients and immunocompetent individuals. Differences were observed in vital signs, symptoms, laboratory results, and radiological findings between the two groups. Pediatric cancer patients showed higher body temperatures and respiratory rates though had a lower incidence of diarrhea. Despite their higher mortality rates, they did not exhibit signs of multisystem inflammatory syndrome or severe organ involvement. Further research is necessary to validate these findings and establish customized care for pediatric cancer patients during the COVID-19 pandemic.

ACE2	Angiotensin Converting Enzyme-2
ALL	Acute lymphocytic leukemia
ALT	Alanine transaminase
AML	Acute myeloblastic leukemia
AST	Aspartate transaminase
CNS	Central nervous system
COVID-19	Coronavirus disease 2019
CRET	Creatinine
IQR	Interquartile range
KAMC-J	King Abdulaziz Medical City, in Jeddah
MIS-C	Multisystem inflammatory syndrome in children
NK	Natural killer cells
PCR	Polymerase Chain Reaction
PICU	Pediatric Intensive Care Unit
PIMS	Pediatric inflammatory multisystem syndrome
PLT	Platelet count
PPE	Personal protective equipment
PT	Prothrombin time
PTT	Partial thromboplastin time
SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2
SBP, DBP	Systolic blood pressure, diastolic blood pressure
SIOP	French Society of Pediatric Oncology
SPSS	Statistical Package for the Social Sciences
WHO	World Health Organization

Ethics approval and consent to participate

Ethics approval was granted by the KAMC International Review Board (REF: IRB/1569/22). Consent to participate not applicable as records were kept private and accessed solely by study authors.

Consent for publication

All authors gave their consent for the publication of this article.

Availability of data and materials

Please contact corresponding author accordingly.

Competing interests

None of the authors has any competing interests.

Funding

None required.

Authors' contributions

Nuha M. Alharbi1 and Fay N. Alnafisi1 contributed as first authors of this study, carrying out all experimental undertakings and analyses. All other authors contributed to the development of article, while Abdullah Baothman also proofread the manuscript.

Acknowledgements

None.

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Clinical Disparities in COVID-19 Presentation, and Outcomes: A Comparative Study of Pediatric Immunocompetent and Cancer Patients, A Single Center Experience

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